Clinical Interventions in Aging
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Physical activity and cognitive function
in individuals over 60 years of age:
a systematic review
Ashley Carvalho''^
Irene Maeve Rea^
Tanyalak Parimon^''
Barry J Cusack^'^
'Department of Public Health, ^School
of Medicine, Dentistry and Biomedical
Science, Queen's University Belfast,
Northern Ireland, UK; ^Research
and Development Service, Veterans
Affairs Medical Center, Boise, ID,
USA; ''Division of Pulmonary and
Critical Care Medicine, ^Division of
Gerontology and Geriatric Medicine,
Department of Medicine, University
of Washington, Seattle, WA, USA
Correspondence: Ashley Carvalho
School of Medicine, Dentistry and
Biomedical Science, Queen's University
Belfast, Northern Ireland, UK BT9 7BL
Email acarvalhoOI@qub.ac.uk
This article was published in the following Dove Press journal:
Clinical Interventions in Aging
1 2 April 2014
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Background: It is unclear whether physical activity in later life is beneficial for maintenance
of cognitive fiinction. We performed a systematic review examining the effects of exercise on
cognitive fiinction in older individuals, and present possible mechanisms whereby physical
activity may improve cognition.
Methods: Sources consisted of PubMed, Medline, CINAHL, the Cochrane Controlled Trials
Register, and the University of Washington, School of Medicine Library Database, with a
search conducted on August 1 5, 20 12 for publications limited to the English language starting
January 1, 2000. Randomized controlled trials including at least 30 participants and lasting
at least 6 months, and all observational studies including a minimum of 100 participants for
one year, were evaluated. All subjects included were at least 60 years of age.
Results: Twenty-seven studies met the inclusion criteria. Twenty-six studies reported a positive
correlation between physical activity and maintenance or enhancement of cognitive function.
Five studies reported a dose-response relationship between physical activity and cognition. One
study showed a nonsignificant correlation.
Conclusion: The preponderance of evidence suggests that physical activity is beneficial for
cognitive function in the elderly. However, the majority of the evidence is of medium quality
with a moderate risk of bias. Larger randomized controlled trials are needed to clarify the asso-
ciation between exercise and cognitive function and to determine which types of exercise have
the greatest benefit on specific cognitive domains. Despite these caveats, the current evidence
suggests that physical activity may help to improve cognitive function and, consequently, delay
the progression of cognitive impairment in the elderly.
Keywords: exercise, cognitive function, elderly
Introduction
An unprecedented growth of the aging population is taking place. For example, in
2000, 28% of adults aged 65 and older were expected to reach at least 90 years; this
number is projected to rise to 47% by 2050, representing a near-doubling of the elderly
population to 80 million. ' The economic impact of an aging population on health care
systems is potentially overwhelming, in particular for age-related disorders such as
dementia. In 2005, approximately 29.3 million individuals with dementia incurred
a cost of US$315 billion worldwide, with the highest costs in North America and
Europe.^ Since then, the global prevalence of dementia has increased to more than
34 million, and the bulk of disease burden is shifting from developed to developing
countries.^ As such, effective interventions to help reduce the prevalence of cogni-
tive disability in the elderly are needed. One possible intervention that deserves
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consideration is physical activity, an adjunct that has many
well established health benefits and may serve to enhance
quality of life.'' However, the effect of exercise on cognitive
function remains controversial. A National Institutes of
Health conference review of age-related cognitive decline
reported a marginal benefit of exercise in one small random-
ized controlled trial (RCT) and eight observational stud-
ies showing a possible decrease in cognitive decline with
exercise.'' A Cochrane review of eleven randomized clinical
trials reported that aerobic exercise improved cognition in
a few domains, including cognitive speed and auditory/
visual attention, in subjects without cognitive impairment.'
Another Cochrane review of exercise in patients with
dementia found only two relevant studies and concluded
that there was insufficient evidence of benefit from exer-
cise in these patients. These reviews did not find sufficient
evidence to endorse exercise as beneficial to cognition, but
were, overall, narrow in scope. However, other reviews have
determined different results; for example, a more recent
review concluded that an exercise regimen of one hour at
least 3 times per week for 6 weeks was beneficial in subjects
with or without cognitive impairment.' We have performed
a systematic review to assess the validity of the current
data, including more recent randomized clinical trials and
observational studies that provide a broad-based view of the
effect of exercise on cognition in elderly persons.
Materials and methods
Studies
All RCTs with at least 30 participants and lasting at least
6 months, and all observational studies (prospective cohort
studies, case-control studies, and longitudinal studies) with
at least 100 participants and lasting at least one year, which
were published in the English language on or after January 1 ,
2000 until August 15, 2012, and met the inclusion criteria
were considered (Table 1).
Participants
Only participants who were 60 years or older were included
in this review. Studies examining the effects of physical
activity in elderly individuals with or without mild cogni-
tive impairment or cognitive disease (such as Alzheimer's
disease or other dementia) were included. Studies including
participants with systemic disorders such as chronic obstruc-
tive pulmonary disease or diabetes, those with traumatic
brain injury, or comorbidities that precluded participation
in exercise programs were excluded.
Table I Characteristics of included studies
Parameters
Number of
References
studies
Type of included studies
Randomized controlled trial
10
8-10,17-21,26,27
Prospective cohort
IS
1 1-16,22-24,55-60
Case-control
1
61
Observational
1
62
Overall quality of included studies
Good
9
9,10,14,17-22
Fair
15
8, II- 13, 15,23,26,27,
55-58,60-62
Poor
3
16,24,59
Overall risk of bias in included studies
Low
8
9,10,14,17,18,20-22
Moderate
16
8,11-13,15,19,23,26,
27,55-58,60-62
High
3
16,24,59
Interventions
Physical activity was considered to be any aerobic or iso-
metric exercise of any intensity, duration, or frequency that
aimed to improve overall physical fitness. For randomized
clinical trials, active interventions such as aerobic exercise,
isometric exercise, health education programs with monitored
exercise sessions, or physical therapy-driven exercise treat-
ments were compared with control groups that received no
intervention (Table 2).
Outcome measures
The primary outcome measurement was cognitive function.
The most commonly used tests included the Mini-Mental
State Examination (MMSE) or Modified Mini-Mental State
Examination (3MS), both of which give a global measure
of cognitive function, and the Cognitive Ability Screening
Instrument (CASI), which indicates the presence or absence
of dementia (Table 2). A neuropsychological test battery
with published criteria (such as the Mayo Clinic Criteria
for dementia) utilized by an expert panel in diagnosing the
presence or absence of dementia was also accepted.
Search methods for study identification
We searched PubMed, Medline, CINAHL, the Cochrane
Controlled Trials Register, and the University of Washington
School of Medicine Library database on August 15, 2012
for studies published in English on or after January 1 , 2000.
We used MeSH terms to find studies of physical activity
including: adaptation, physiological/physiology*, exercise/
physiology*, and physical fitness/physiology*. To reduce our
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Clinical Interventions in Aging 2014:9
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Physical activity and cognitive function in individuals aged over 60 years
findings to studies that measured cognition or incidence of
cognitive disease and physical fitness, we searched using the
following MeSH terms: cognition, cognitive disease, cogni-
tion disorders/prevention and control, cognition/physiology*,
brain/physiology*, memory/physiology*, motor activity/
physiology*, neuropsychological tests, dementia, and
Alzheimer's disease. To further reduce our findings to studies
that focused on elderly human subjects, we searched using
the MeSH terms: humans, elderly, aged, aging, old, older,
and geriatric.
Data collection
Two reviewers screened the titles and abstracts of all studies
identified by the search (7 1 studies) and irrelevant studies
were excluded. Relevant papers were then assessed in full
for inclusion eligibility.
Quality assessment
Two reviewers assessed the methodological quality of the
selected studies. The Agency for Healthcare Research and
Quality Methods Reference Guide for Effectiveness and
Comparative Effectiveness Reviews was used to perform
quality assessment of the trials. These criteria include
information on sampling method, outcome measurement,
intervention, and reporting of biases and limitations. A sum-
mary of these criteria is presented in Table S 1 .
Results
Description of studies
Seventy-one studies were identified using the database as
described in the Materials and methods section. After removal
of duplicates, 57 full-text articles were assessed for eligibility
(Figure 1). Thirty studies were excluded, leaving 27 studies
that were eligible for review according to the prespecified
criteria (Figure 1). A total of 30,572 subjects over 60 years
of age were included in the 27 studies that met our inclusion
criteria. The characteristics of the studies included in this
review are described in Tables 1, 2, and 3. The 30 excluded
studies are described in Table S2.
Type of included studies,
and quality and bias
Fifteen prospective cohorts, ten RCTs, one case-control
study, and one observational study met the criteria for review
(Table 1). Eight studies were considered to be of high quality.
One study,* an RCT, was considered to be of fair quality, rather
than high, because approximately 12% of patients dropped out
Records identified through
database searching
(n=71)
Additional records identified
through other sources
(n=0)
Records after duplicates removed
(n=57)
Records screened
(n=57)
Records excluded
(n=0)
Full-text articles
assessed for eligibility
(n=57)
Full-text articles
excluded, with reasons
(n=30)
Studies included in
systematic review
(n=27)
Figure I Description of studies v/hich were identified, screened, and included in
the systematic review.
of the study and could not be assessed. The majority of studies
(15/27) were of fair quality while three were considered poor
quality. The overall risk of bias was moderate for the majority
of the studies (16/27) with eight considered low risk and three
at high risk of bias (Table 1). Seven of ten RCTs included in
the review were generally of higher quality and exhibited lower
bias overall (Table 1). However, the RCT evidence included
in this review displayed potential bias in the form of lack of
allocation concealment and lack of assessor blinding, as well
as lack of participant blinding, since participants were ran-
domized into either a physical activity group or an education/
noninterventional control group. In these studies, the evidence
tended to be of lower quality with potentially higher bias due
to possible uru-eliable self-reporting, potential influence of
interviewers, and use of questionnaires and interviews to assess
physical activity rather than direct measurements.
Selection bias
Most of the studies included in this review were at risk of
selection bias, because the participants were largely drawn
from specific population samples (hospital, city, region).
Selection bias may also have occurred due to the fact that
the decision to partake in physical activity may be linked to
potentially confounding lifestyle choices. Further, follow-
up visits were required for most of the studies, and would
require the ability to commute to study centers. Potential
participants were excluded if they had chronic disease, such
as cardiovascular disease, pulmonary disease, diabetes,
physical disability, or depression. Therefore, the study data
cannot be extrapolated to such individuals.
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Table 2 Design, methods, interventions and assessment, and outcome measures in included studies
Source and
study design
Methods
Participants
Buchman et al^^
Prospective study
Busse et aC'
RCT
Bixby et al"
Observational
Cassilhas et al"
RCT
Geda et al"
Case-control
Klusmann et al"
RCT
Total daily physical activity v^as measured with
actigraphs at baseline. Late-life physical, social, and
cognitive activities were assessed by self-report and
by the 1985 National Health Interview Survey
questions at baseline and follow-up.
Follow-up: annual assessment for 3.S±I.S4 years
Participants were randomized to a control group
(n= 1 4) or a treatment group (n= 1 7).
Cognitive status was assessed at baseline and follow-
up using a neurocognitive test battery. Neither the
participants nor the outcome assessors were blinded,
and the use of allocation concealment is unclear.
Follow-up: 3, 6, and 9 months
Participants were recruited from a retirement
community through posted flyers, closed-circuit
television announcements, and investigator
presentations.
Physical activity levels were assessed using the YPAS.
Cognitive and inhibitory executive function was
assessed by the Stroop Color and Word Test.
Follow-up: not applicable
Participants were randomized to 3 groups: a control
group (n=23), moderate exercise group (n=l9), and
high exercise group (n=20).
Use of blinding and allocation concealment in the study
is unclear.
Physical fitness was assessed at baseline and follow-up
by the one RM test.
Cognitive status was assessed at baseline and follow-up
using a neuropsychological test battery.
Follow-up: 24 weeks
Participants underwent stratified random sampling in to
case or control group.
Physical fitness was assessed through self-reporting at
baseline.
Cognitive status was assessed at baseline and follow-up
using a neuropsychological test battery and visuospatial
skills.
Follow-up: 4 years
This study enrolled German-speaking women from Berlin.
Eligible subjects were randomized into 2 intervention
groups (n=9 1 for exercise group, n=92 for computer
group), and a control group (n=76).
12 participants (5 in the exercise group and 7 in the
computer group) refused to participate after being
informed about their group assignment and withdrew
consent before treatment started.
A complete neuropsychological assessment and
physical evaluation at baseline and 6 months.
Follow-up: 6 months
716 subjects
I 14 males and 602 females
8 1 .6±7. 1 2 years
Inclusion criteria: eligible participants of Rush Memory and Aging
Project.
Exclusion criteria: Presence of clinical AD dementia and non-AD
dementia; unable to have at least one follow-up cognitive testing
3 1 subjects
8 males and 23 females
62-86 years
Inclusion criteria: No programmed physical exercise 6 months
prior to selection; subjective memory complaints; normal CDS
and MMSE; changes in objective memory test; preserved function
in instrumental and basic activities of daily living.
Exclusion criteria: dementia, depression, anxiety disorders, head
trauma or stroke within one year, substance abuse, unstable
cardiovascular disease
1 20 subjects
38 males and 82 females
65-92 years
Retirement community residents recruited through posted
flyers, closed-circuit television announcements, and investigator
presentations.
Inclusion criteria: above average intelligence; stable patterns of
physical activity during a 3— 5-year period before the study.
Exclusion criteria: depression, dementia
62 subjects
All males
65-75 years
Inclusion criteria: not described.
Exclusion criteria: cardiovascular disease; psychiatric conditions;
use of psychotropic drugs; <8 years of schooling; dementia
(MMSE score <23)
1 ,324 subjects
681 males and 633 females
70-89 years
Participants of the Mayo Clinic Study of Aging
Cases: (n=l98) cases with mild cognitive impairment based on:
concern expressed by a physician or nurse; cognitive impairment
in one or more tested domains; ability to participate in normal
functioning activities; and free of dementia.
Controls: (n=l,l26) cases with normal cognitive function
according to published normative criteria for the community
259 subjects
All female
Age >70 years
Eligibility criteria: being unfamiliar with the computer and
exercising less than one hour per week.
Exclusion criteria: severe visual or hearing impairment; a
previous or current diagnosis of depression or psychosis; any
other neurological or medical disorder that would interfere with
cognitive performance or preclude successful participation in the
intervention programs
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Physical activity and cognitive function in individuals aged over 60 years
Interventions
Cognitive function nneasurennents
None
A computer-scoring battery of 19 tests
Diagnosis of AD and non-AD was performed by
clinicians using National Institute of Neurological and
Communicative Disorders, Stroke-Alzheimer's Disease
and Related Disorders Association Criteria
Treatment group: a one-hour biweekly training session for 9 months with 6
resistance-training exercises per session. Loads progressively increased in series
of 1 2, 1 0, and 8 repetitions.
Control group: no intervention
Rivermead Behavioral Memory Test
Wechsler Adult Intelligence Scale
Direct and Indirect Digit Span
Memory Complaints Scale
Cambridge Cognitive Test
None
Physical fitness assessment: YPAS and weekly energy expenditure (beyond basal
metabolic rate).
Stability in physical activity levels for 3-5 years prior to the study assessment: a health
history questionnaire.
Cognitive function assessment: Kaufman Brief Intelligence Test and Stroop Color and
Word Test
Kaufman Brief Intelligence Test
Stroop Color and Word Test
Moderate exercise group: Three one-hour sessions/week (lO-minute cycling warm-up,
stretching exercises and weight training using loads of 50% of one RM and alternating
segments with two series of 8 repetitions for each segment).
High exercise group: Three one-hour sessions/week (lO-minute cycling warm-up,
stretching exercises, and weight training using loads of 80% of one RM and alternating
segments with two series of 8 repetitions for each segment).
Control group: one weekly training session consisting of warm-up and stretching
exercises, but no overload training
Wechsler Adult Intelligence Scale III
Wechsler Memory Scale-Revised
Toulouse-Pieron concentration attention test
Ray-Osterrieth complex figure
None
Physical fitness assessment: a self-reported questionnaire derived from the 1 985
National Health Interview Survey and the Minnesota Heart Survey intensity codes.
Cognitive function assessment: Mayo Clinic criteria for mild cognitive impairment
Mayo Clinic criteria for mild cognitive impairment
Exercise group: exercise program consisted of aerobic endurance, strength, and
flexibility training, as well as practice of balance and coordination.
Computer group: heterogeneous and multifaceted themes including creative matters,
coordinative and memory tasks, eg, operating with the common software and hardware,
writing, playing, calculating, surfing on the Internet, emailing, drawing, image editing, and
videotaping.
Control group: continued their habitual life
Neuropsychological assessment
RBMT, FCSRT, TMT, and Stroop Test
{Continued)
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Table 2 (Continued)
Source and
study design
Methods
Participants
Ku et al"
Prospective study
Larson et al"
Prospective study
Laurin et al'^
Prospective study
Lytle et al"
Prospective study
Middleton et al'^
Prospective study
Miu et al'
RCT
Mortimer et al''
RCT
Physical activity and activities of daily living were
assessed through questionnaires. The survey was
conducted every 3—4 years from 1996 to 2007.
Cognitive performance wzs assessed using the
lO-item SPMSQ.
Follow-up: I I years
The current study was to examine the temporal
relationship of physical exercise preceding
development of dementia.
Physical activity was assessed at baseline by an interview.
Cognitive function was assessed at baseline and follow-
up using the CASI.
Follow-up: biennially for 6.2 years
Physical activity and cognitive status were assessed
at baseline and follow-up.
Follow-up: 5 years
Physical activity was assessed at baseline through
self-reporting and cognitive function was assessed
at baseline and at follow-up using the MMSE.
Follow-up: 2 years
Physical fitness was assessed at baseline and follow-up
by using a battery of fitness and metabolism tests, and
cognitive function was assessed at baseline and follow-
up by using the 3MS.
Follow-up: 2 or 5 years
Participants were randomized to a control group
(n=49) or a physical activity treatment group (n=36).
Physical fitness was assessed at baseline and follow-up
by using a battery of physical function tests.
Cognitive status was assessed at baseline and follow-up
using the MMSE and the ADAS-Cog.
Follow-up: 3, 6, 9, and 12 months
Participants were randomized into 4 groups: group I ,
Tai Chi (n=30); group 2, walking (n=30); group 3,
social (n=30); and group 4, no intervention (n=30)
for a total of 40 weeks.
1 , 1 60 subjects
586 males and 574 females, a67 years
Inclusion criteria: participants of the longitudinal Survey of Health
and Living Status of the Elderly (Taiwan Department of Health)
aged >67 years.
Exclusion criteria: not stated
1 ,740 subjects
693 males and 1 ,047 females, a65 years
Participants of the ACT study
Inclusion criteria: ACT study participant with CASI score above
the 25th percentile; residing in the Seattle area at time of study.
Exclusion criteria: pre-existing dementia or cognitive impairment
4,6 1 5 subjects
1 ,83 1 males and 2,784 females, a65 years
Participants of the 1991-1992 Canadian Study of Health and
Aging, a prospective cohort study of dementia.
Inclusion criteria: age >65 years and registered in the 1991 — 1992
Canadian Study of Health and Aging.
Exclusion criteria: dementia
1,146 participants
722 males versus 424 females, £65 years
Participants of MoVIES
Inclusion criteria: Residing in the community of Monongahela
Valley (not in a skilled care facility) at time of recruitment; fluent
in English and having at least a 6th grade education.
Exclusion criteria: not described
1 97 subjects
Sex not stated
70-79 years
Participants of the Health ABC study.
Inclusion criteria: ability to walk 0.4 km, climb ten stairs, and
perform basic activities of daily living without difficulty; no plans
to leave the area for the next 3 years.
Exclusion criteria: life-threatening illness; mobility limitations;
cognitive impairment (3MS score <80)
85 participants
Sex not clearly stated
£65 years
Participants of the memory clinic at a regional hospital in Hong Kong
Inclusion criteria: mild-to-moderate dementia; MMSE 10—26; age
>60 years; community-dwelling; ambulatory, having a caregiver
willing to participate and escort the patient to the hospital for
training and assessment.
Exclusion criteria: severe dementia or MMSE score < 10
1 20 subjects
40 males and 80 females
60-79 years
Inclusion criteria: participants of Jingansi Temple Community of
Shanghai, China aged 60-79 years.
Exclusion criteria: history of stroke, Parkinson's disease, or
other neurological disease; inability to walk unassisted for
2 km or maintain balance with feet side-by-side or semi-
tandem for 10 seconds each; education-adjusted Chinese
MMSE <26; cardiovascular disease; musculoskeletal conditions;
contraindication for MRI; unable to participate in the full study
and regular vigorous exercise or Tai Chi practice
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Physical activity and cognitive function in individuals aged over 60 years
Interventions
Cognitive function measurennents
None
Physical activity assessment: questionnaire survey at baseline.
Cognitive performance assessment: SPMSQ that was validated for the Chinese version
of the MMSE
Ten-item SPMSQ
None
Physical exercise assessment: subject interview (number of days per week and number
of hours per session) during the past year. Participants who exercised at least 3 times
a week were classified as regular exercisers.
Cognitive status and incident dementia assessment: CASI
CASI (score <86 resulted in a neuropsychological
clinical evaluation)
DSM-IV criteria for dementia (25 criteria in total)
None
Physical fitness assessment: a self-administered questionnaire by mail.
Cognitive function assessment: 3MS
3MS score (a reduction of aS points indicative of
cognitive decline)
None
Physical activity assessment: a standardized questionnaire.
Exercise was classified as aerobic (high level) or anaerobic (low level).
Cognitive status assessment: MMSE
MMSE score (drop of at least 3 points between
assessments was indicative of cognitive decline)
None
Physical fitness assessment: doubly-labeled water techniques for total energy expenditure
measurement between baseline and follow-up; a respiratory gas analyzer for measuring
resting metabolic rate; an interviewer-administered questionnaire at first visit to
ascertain physical activity habits over the past 7 days.
Cognitive status assessment: 3MS score
3MS score (a decline of at least one standard deviation
or 9 points from baseline to the most recent follow-up
visit indicated cognitive decline)
Treatment group: aerobic exercise training supervised by a physiotherapist, including
treadmill, bicycle, and arm ergometry, and 1 0-minute flexibility training prior to each
session. Training sessions occurred biweekly and lasted 45—60 minutes each. Total
duration of treatment was 3 months.
Control group: no intervention
MMSE
ADAS-Cog
Tai Chi: practising 3 times per week (20 minutes warm-up, 30 minutes of Tai Chi
practice, and 10 minutes cool-down).
Walking: a 400 m circular walking ( 1 0 minutes of warm-up, 30 minutes of brisk walking,
and 10 minutes of cool-down exercise).
Social interaction: meeting with group leader for one hour 3 times per week.
Brain volume assessment: MRI at baseline and at the end of intervention (40 weeks).
Cognitive assessment: neuropsychological battery at baseline, 20 weeks, and 40 weeks
Brain volume using MRI
Neuropsychological battery test
(Continued)
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Table 2 (Continued)
Source and
study design
Methods
Participants
Muscari et aP'
RCT
Nagamatsu et aP'
RCT
Nguyen et aP'
RCT
Podewils et aP'
Prospective study
Ravaglia et aP^
Prospective study
Scarmeas et aP'
Prospective study
Schuit et aP"
Prospective study
Subjects were randomized into a control group (n=60)
and a physical activity treatment group (n=60).
Cognitive status was assessed at baseline and follow-up
by using the MMSE.
Follow-up: 1 2 months
Subjects were randomized, single-blinded into:
twice-weekly resistant training (n=28); twice-weekly
aerobic training (n=30); or twice-weekly balance
and tone training (control) group (n=28).
Follow-up: 6 months
Participants were randomly divided into 2 groups;
Tai Chi (n=48) and control (n=48) group. Experienced
Tai Chi instructors were selected by investigators to
teach classes. Outcome measures were assessed at
baseline and the end of 6-month Tai Chi training.
Follow-up: 6 months
Physical activity information was assessed at baseline
and follow-up by interview and the 3MS, respectively.
Follow-up: annually for 5.4 years
Physical activity was self-reported at baseline by using
a questionnaire and cognitive status was measured at
baseline and follow-up by using a neuropsychological
test battery. Participants were screened for incident
dementia using an extensive neuropsychological test
battery.
Follow-up: 4 years
Physical activity was self-reported at baseline, and cases
of incident dementia were identified at each follow-up
using a neuropsychological test battery in conjunction
a consensus diagnosis among an expert panel based on
the DSM-IV criteria.
Follow-up: every 1 .5 years for 1 5 years
Physical activity was assessed at baseline through self
reporting. Cognitive function was assessed at baseline
and follow-up using the MMSE.
Follow-up: 3 years
1 20 subjects
62 males and 58 females
65-74 years
Inclusion criteria: participants of the Pianoro Study, aged 65-74
years.
Exclusion criteria: Presence of any cardiovascular disease and
the followings; MMSE score <24; BMI < 18 or >32; systolic BP
> 1 80 or < I 10 mmHg; diastolic BP < I 1 0 mmHg; malignancy;
moderate or severe respiratory insufficiency; severe arthrosis;
recent fractures, palsy or relevant neuromotor deficits;
hemoglobin < I I g/dL; aortic aneurysm >3.5 cm
86 subjects
All females
70-80 years
Inclusion criteria: female, aged 70-80 years, with probable mild
cognitive impairment.
Exclusion criteria: not described
1 02 subjects
48 males and 48 males
60-79 years
Inclusion criteria: MMSE score >25; having no experience in Tai
Chi.
Exclusion criteria: serious diseases such as symptomatic coronary
diseases, angina, arrhythmia, orthostatic hypotension, and
dementia
3,375 subjects
1,350 males and 2,025 females
£65 years
Inclusion criteria: enrollment in Cardiovascular Health
Cognition Study; residing in Sacramento County, CA,
Washington County, MD, Forsyth County, NC, or Pittsburgh,
PA, USA.
Exclusion criteria: dementia
749 subjects
348 males and 401 females, £65 years
Inclusion criteria: individuals £65 years in the Conselice Study of
Brain Ageing.
Exclusion criteria: per the Conselice Study of Brain Ageing
1 ,880 participants
587 males and 1 ,293 females
70-82 years
Participants were recruited through the WHICAP from a sample
of Medicare beneficiaries in northern Manhattan.
Inclusion criteria: WHICAP participants.
Exclusion criteria: not described
347 participants
All males
70-80 years
Inclusion criteria: participants of the Zutphen Elderly Study, the
Netherlands.
Exclusion criteria: per the Zutphen Elderly Study
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Physical activity and cognitive function in individuals aged over 60 years
Interventions
Cognitive function measurennents
Treatment group: 1 2 months of 3 one hour-long sessions per week of supervised
endurance exercise training in a community group.
Control group: education to improve lifestyle and self-administered programs to increase
physical activity
MMSE score (decrease of greater than one point was
indicative of cognitive decline)
Resistant training group: a Keiser pressurized air system and free weights were used.
Aerobic training group: an outdoor walking program.
Balance and tone training (control) group: stretching, range of motion, balance exercises,
and relaxation technique
Treatment group: a 60-minute Tai Chi session twice a week for 6 months. The session
consisted of a IS-minute warm-up and cool-down period.
Control group: no intervention, maintained daily routine activities and not to begin any
new exercise program
Primary outcome measure:
Stroop Test performance
Secondary outcome measures: TMT,
Verbal Digits Test
Memorizing face-scene pairs
Everyday Problem Test
TMT for motor speed and visual attention
None
Physical activity assessment: modified Minnesota Leisure Time Activity Questionnaire.
Cognitive status assessment: 3MS or the Telephone Interview for Cognitive Status for
participants who did not receive a clinical evaluation
3MS score (<80 within the last 2 visits; decline of at
least 5 points within the follow-up period;
Telephone Interview for Cognitive Status score of <28;
diagnosis of dementia that was documented in medical
records
None
Physical fitness assessment: Paffenbarger Physical Activity Questionnaire.
Cognitive status assessment: CDS, MMSE, and MDB for use in rural and poorly
educated subjects
MMSE (cognitive impairment defined as a score of <24)
MDB
None
Physical activity assessment: two versions of the Godin leisure time exercise
questionnaire.
Cognitive status assessment: a neuropsychological test battery testing the domains
of memory, language, reasoning, processing speed, and visual-spatial ability
The decision of expert panel composed of neurologists
and neuropsychologists in according to DSM-IV criteria
None
Physical fitness assessment: a self-administered questionnaire at baseline. Physical activity
was categorized as either "maximal I hour/day" or "more than I hour/day".
Cognitive status assessment: MMSE at baseline and follow-up
MMSE (drop in 3 points indicative of cognitive decline)
(Continued)
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Table 2 {Continued)
Source and
Methods
Participants
study design
Smiley-Oyen et aP'
Participants were randomized to an aerobic physical
62 subjects
RCT
activity (Cardio, n=28) group or a strength-
16 males and 41 females
and-flexibility (Flex-Tone, n=29) training group.
65-79 years
Physical fitness was assessed at baseline and follow-up
Residents of the mid-western US
using a battery of fitness tests, and cognitive status
Inclusion criteria: living independently; able to exercise safely.
was assessed at baseline and follow-up by using a
Exclusion criteria: various health-related reasons (autoimmune
battery of neurocognitive tests.
disease, cancer diagnosis within the previous 5 years, or
Follow-up: at 4 and 10 months
conditions which may be exacerbated by strenuous exercise);
being "too-fit" ( participation in exercise >3 times/week at
>40% of their heart rate reserve), or participant's aerobic fitness
level above the 75th percentile for their age and sex by a time
walking test)
Taaffe et al^«
Physical activity was assessed at baseline by
2,263 subjects
Prospective study
self-reporting and performance.
All males
The incident dementia was assessed at baseline
71-92 years
and follow-up using CASI.
Inclusion criteria: enrollment in the Honolulu-Asia Aging Study;
Follow-up: at 3 and 6 years
Japanese-American men born between 1900 and 1919 living on
the island of Oahu, Hawaii.
Exclusion criteria: dementia
Van Gelder et al"
Physical activity was assessed at baseline and at follow-
295 subjects
Prospective study
up by using a self-administered questionnaire, and
All males
cognitive status was assessed at baseline and at follow-
70-90 years
up by using MMSE.
Inclusion criteria: participants of the Surviving cohorts of the
Follow-up: at 5 and 1 0 years
Seven Countries Study in Europe.
Exclusion criteria: poor health (myocardial infarction, stroke,
diabetes, or cancer); severe cognitive impairment (MMSE <I8)
Wang et al'"
Physical fitness was assessed at baseline by using a
2,228 subjects
Prospective study
physical function test battery and cognitive function
863 males versus 1,365 females
was assessed at baseline and follow-up by using
a6S years
a neurocognitive test battery.
Inclusion criteria: participants of the Adult Changes in Thought
Follow-up: biennially through October 2003
study (1994-1996) Exclusion criteria: CASI <86; dementia;
(8-10 years)
invalid measurements on the cognitive performance test or
physical performance test at baseline; persons without a follow-
up examination
Wang et al"
Leisure activity levels and cognitive status assessment
1,463 subjects
Prospective study
were performed at baseline and follow-up.
744 males and 7 1 9 females
Follow-up: mean 2.4 (2.3-2.6) years
£65 years
Participants of a longitudinal population-based study of aging in
the People's Republic of China between 2003 and 2005.
Inclusion criteria: residents aged £65 years in the study regions.
Exclusion criteria: baseline global cognitive score in the bottom
10%; physical disability
Williamson et al'
Subjects were randomized to a control group (n=52)
1 02 participants
RCT
or a physical activity treatment group (n=SO).
50 males and 72 females
Physical fitness was assessed at baseline and follow-
70-89 years
up using a battery of performance tests for balance.
Participants of the LIFE-P study
walking speed, and sitting-to-standing time.
Inclusion criteria: sedentary lifestyle; ability to walk 400 m in 1 5
Cognitive function was assessed at baseline and
minutes without resting or assistance; SPPB score <9.
follow-up by using a neuropsychological test battery.
Exclusion criteria: MMSE <2 1 ; life expectancy of < 1 2 months;
Follow-up: 12 months
heart disease; severe neurological conditions such as Parkinson's
disease during time of study
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Physical activity and cognitive function in individuals aged over 60 years
Interventions
Cognitive function measurennents
Cardio group: a 10-month of tri-weekly training sessions (lO-minute warm-up,
25—30 minutes of aerobic exercise on the equipment of the participant's choice (treadmill
stair-stepping machine, stationary cycle, and elliptical machine), and
a lO-minute cool down.
Flex-Tone group: A 10-month tri-weekly training sessions (lO-minute warm-up,
25—30 minutes of strength, flexibility, and balance exercises (yoga, Tai Chi, Flex bands,
free hand weights, resistance weight training machines, and stability balls), and
a lO-minute cool down; 8-10 exercises of 1 — 15 repetitions each were performed
Reaction time tests including simple reaction time,
8-choice reaction time, 8-choice incompatible reaction
time, and Go/No-Go reaction time
Stroop Color and Word Test
Wisconsin Card Sort Test
None
Physical activity assessment: a self-reported questioner.
Physical function assessment: four performance tasks, ie, timed walk, sitting-to-standing
time, grip strength, and balance.
Cognitive status assessment: CASI used as the initial assessment. For CASI <74,
subjects underwent a second phase of screening (a repeat CASI and administration
of the IQCODE). Men with an IQCODE score of >3.6 underwent a third phase
assessment (a standardized interview and neuropsychological battery, neurological
examination, neuroimaging, and blood testing)
None
Physical fitness assessment: a self-administered questionnaire.
Physical activity was categorized into four groups: <30, 3 1—60, 6 1 — 1 20, and
> 1 20 minutes per day.
Cognitive status assessment: MMSE
CASI (scores <74 indicative of possible dementia)
IQCODE (scores <3.6 indicative of probable dementia)
Diagnoses were finally decided by consensus of an
appointed expert panel
MMSE (scores < 1 8 indicative of cognitive decline)
None
Physical fitness assessment: Four different physical performance tests (timed
walk, seating-to-standing time, standing balance, grip strength).
Cognitive function assessment: CASI
CASI (score >86 were categorized as dementia-free)
None
Leisure activities assessment: a self-reported questionnaire in predefined list of mental,
physical and social activities.
Cognitive assessment: face-to-face interviews at the home of subjects using the
followings; CSID, Word List Learning, Word List Recall, lU Story Recall, Animal Fluency
Test, lU Token Test
Global cognitive function: CSID
Episodic memory: Word List Learning, Word List
Recall, ID Story Recall
Language: Animal Fluency Test
Executive function: ID Token Test
Treatment group: physical activity intervention consisting of a combination of aerobic,
strength, balance, and flexibility exercises divided into 3 phases: adoption (weeks 1-8),
transition (weeks 9—24), and maintenance (week 25 to end of study).
Control group: health education intervention designed to provide attention and health
education to participants. Participants met in small groups weekly for the first 26 weeks
and then monthly to the end of the study
Digit Symbol
Substitution Test
Modified Stroop Test
MMSE
The Rey Auditory Verbal Learning Test
(Continued)
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Table 2 (Continued)
Source and
Methods
Participants
study design
Yaffe etal"
Physical activity was self-reported at baseline through
5,925 subjects
Prospective study
both interview and questionnaire. Cognitive function
All females
was assessed at baseline and follow-up using the 3MS.
a6S years
Follow-up: 6-8 years
Inclusion criteria: participants of the Study of Osteoporotic
Fractures (a prospective study for risk factors of fractures in
Baltimore, MD, Minneapolis, MN, Pittsburgh, PA, or Portland,
OR, USA).
Exclusion criteria: black women: unable to walk without
assistance: bilateral hip replacements; baseline cognitive
impairment; baseline physical limitations
Abbreviations: 3MS, Modified Mini-Mental State; ACT, Adult Changes in Thought; ADAS-Cog, Alzheimer's Disease Assessment Scale-Cognitive subscale; BMI, body mass index;
BP, blood pressure; CASI, Cognitive Abilities Screening Instrument; CSID, Community Screening for Dementia; DSM-iV, Diagnostic and StaUstical Manual of Mental Disorders, Fourth
Edition; Health ABC, Health, Aging, and Body Composition; CDS, Geriatric Depression Scale; YPAS, Yale Physical Activity Survey; LIFE-P, Lifestyle Interventions and Independence
for Elders Pilot; MDB, Mental Deterioration Battery; MMSE, Mini-Mental State Examination; RBMT, Rivermead Behavioural Memory Test; FCSRT, Free and Cued Selective
Reminding Test; MRI, magnetic resonance imaging; TMT, Trail Making Tests; SPMSQ, Short Portable Mental Status Questionnaires; 3GM, Modified Mini-Mental Status Examination;
MoVIES, Monongahela Valley Independent Elders Survey; SPPB, Short Physical Performance Battery; RCT, randomized controlled trial; WHICAP, Washington Heights-lnwood
Columbia Aging Project; IQCODE, Informant Questionnaire on Cognitive Decline in the Elderly; AD, Alzheimer's disease; RM, repetition maximum; lU, Indiana University.
Effect of physical activity intervention
Twenty-seven studies (Table 1) met the inclusion criteria
for this review. Of these, 26 studies reported a significant
association between physical activity and cognitive function
in late life (Tables 3 and 4). Of the ten RCTs, nine showed
a positive correlation and one showed a nonsignificant
correlation.' Although these studies included both male and
female subjects, one RCT by Klusmann et al'" enrolled only
elderly healthy female subjects. As compared with controls,
the authors also found a significant benefit of physical exercise
(aerobic training with a bicycle ergometer or treadmill) in
this elderly female population. Therefore, the majority of the
studies concluded that physical activity in later life confers a
protective effect on cognition in elderly subjects. Additionally,
there were five studies"""" that reported a dose-response asso-
ciation between physical activity and cognitive function.
Discussion
This review examined the effect of physical activity in late
life on age-related cognitive decline in older individuals with
normal cognitive function or mild cognitive impairment at
baseline. When selecting studies for review, the assumption was
made that there is no difference in effect on cognition between
different physical activities, ranging from aerobic to isometric
exercises. As such, all types of physical activity program
interventions were accepted in the study selection process. The
data indicate that this assumption was generally connect; 26 of
27 studies showed a significant association between physical
activity and cognitive decline, whereby an increased level of
physical activity resulted in attenuation of cognitive decline and
cognitive disease (Tables 3 and 4). hi the ten RCTs evaluated
in this review, the different interventions included aerobic and
isometric exercise, weight training, andTai Chi. Eight of these
studies showed a significant outcome benefit, with one study
showing a nonsignificant correlation (Table 4). Although these
trials were not designed to determine a threshold effect or dose-
response effect, there were five prospective studies suggesting
a dose-response relationship in the level of benefit found with
exercise,"""" thus providing additional credence to the specific-
ity of the effects of exercise on cognitive function.
Implications of evidence quality
Despite the preponderance of positive studies, only nine of
the 27 studies were considered to be of high quality and the
overall risk of bias was moderate in 16 studies (Table 1).
Many studies included in this review relied on self-reporting
to assess exercise habits, rather than using a more objective
means of measuring physical activity.
In the studies evaluated in this review, outcome measures
of cognitive performance were wide-ranging and measured
different aspects of cognitive ftinction (Table S3). Several
studies used a neuropsychological test battery to test multiple
aspects of cognitive function, while other studies used only
one or two cognitive tests. Data heterogeneity may have con-
founded identification of the domains of cognitive fiinction
that were most affected by exercise. We standardized the cog-
nitive metrics, inclusion criteria, and outcomes in this review
as much as possible, which may have enabled us to ascertain
an association between exercise and a few specific domains
of cognitive function, such as the MMSE and Cognitive
Inhibition (Stroop Color and Word Test). In the nine studies
considered to be of higher quality, seven were RCTs' '" ""^'
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Physical activity and cognitive function in individuals aged over 60 years
Interventions Cognitive function measurennents
None 3MS score (cognitive decline defined as a decrease in 3
Physical fitness assessment: a self-reported questionnaire and a modified Paffenbarger or more points from baseline to follow-up)
scale (to quantify frequency and duration of weekly participation in 33 different physical
activities) administered by trained interviewees.
Cognitive function assessment: 3MS
and two were prospective studies. "'■^^ In these studies, a posi-
tive correlation was evident between physical activity in later
life and cognition in the elderly subjects evaluated.
Similarly, the types of physical activity interventions used
in the studies reviewed were wide-ranging, from aerobic or
isometric physical activity, or combinations of both. Given
the variability in physical activity interventions and the mea-
sures of cognitive function, it was not possible to determine
a distinct relationship between specific types of physical
activity and improvements in specific cognitive domains. As
such, better standardization of the types of physical activity
interventions could have clarified the specific causal relation-
ships more effectively.
The durations of the included studies ranged from 6 months
to several years. It is possible that improvements in some
aspects of cognitive function occur shortly after completion of
an exercise program, while improvements in other aspects may
take several months or years to develop. For example, when
using the 3MS or MMSE as one of the outcome measures, there
was only one study showing a positive effect at 12 months^"
whereas the other two did not;* ' and five studies demonstrated
the positive impact of exercise on cognitive function over the
course of more than 12 months. The positive effect of
exercise on cognitive speed^*"'^' and cognitive inhibitory fiinc-
tion^' can be observed as early as 6 months. These observations
highlight the time-specific effect of physical activity on each
cognitive domain. Of interest, a study by Segal et aP^ found
that the acute effects of exercise enhance learning ability in
patients with mild cognitive impairment and subjects with
normal cognition. These investigators postulated that exercise
could function as a stimulus for memory consolidation due to
its stimulatory effects on the locus coeruleus and consequent
release of norepinephrine. They found that exercise, conducted
acutely after a period of learning, significantly increased the
release of endogenous norepinephi-ine in both types of study
subjects and resulted in retrograde enhancement of memory.^*
As such, acute exercise, associated with periods of learning,
may be a positive therapeutic intervention for cognitive decline
in elderly subjects. In future research, it would be important to
determine which forms of exercise affect specific domains of
cognition and, also, the latency and duration of effect.
An exclusion criterion for this review was the presence
of specific underlying conditions or diseases in the study
population (such as chronic obstructive pulmonary disease,
diabetes, traumatic head injury, cardiovascular disease, or
depression). Therefore, our findings cannot be extrapolated
to individuals with chronic underlying conditions in whom
improvements in cognitive performance following a program
of physical activity may be diminished or not apparent. For
example, Hoffman et aF' published an RCT in which a pro-
gram of physical activity failed to improve neurocognition
in elderly subjects with clinical depression. This also has
implications when assessing the overall effectiveness of physi-
cal activity in later life on cognitive performance in the very
elderly, since a significant proportion of this population suffers
from chronic conditions that may impede improvements in
cognitive function following a physical activity regimen.
Neural plasticity: possible mechanisms
for effect of exercise on cognition
Decline in cognitive fimction is one of the hallmarks of the
aging process. The concept of neuronal structural plasticity
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Table 3 Results of included studies
Source and study
design
Results
Buchman et zP^
Prospective study
Busse et al"
RCT
Bixby et al"
Observational
Cassilhas et al'°
RCT
Geda et al"
Case control
Klusmann et al'°
RCT
Ku et al"
Prospective study
Larson et al''
Prospective study
Laurin et aP
Prospective study
Lyde et al"
Prospective study
Middleton et al'^
Prospective study
Miu et al'
RCT
Mortimer et al"
RCT
Muscari et aP'
RCT
Nagamatsu et aP'
RCT
Nguyen et al"
RCT
Podewils et al"
Prospective study
Total daily physical activities were associated with incident Alzheimer's disease (hazard ratio 0.477, 95% confidence
interval 0.273-0.832).
After 9 months, the physical activity group showed a significant increase in RBMT score from pre-test to post-test, while
the control group showed no increase.
A small but significant association between physical fitness and executive function in the sample of older men and women.
Both moderate-intensity and high-intensity resistance exercise programs had equally beneficial effects on cognitive
functioning. However, the study was not able to identify a dose-response relationship between level of exercise and level
of cognitive functioning.
The odds ratio for any frequency of exercise of at least a moderate level in late life was 0.68, suggesting that any frequency
of moderate-intensity exercise performed in late life is associated with a reduced odds ratio of mild cognitive impairment.
Both the exercise group (mean ± SD change 2.09±2.66, P<0.00 1 ) and the computer group (mean ± SD change 1 .89±2.88,
P<0.00 1 ) showed improved delayed story recall. They maintained performance in delayed word recall and working
memory (time measure) as opposed to the control group that showed a decline (mean ± SD change —0.9 1 ±2. 1 5, P=0.00 1 ,
and mean ± SD change 0.24±0.68, P=0.04, respectively). In conclusion, in older healthy women, exercise and computer
classes seem to generate equivalent beneficial effects.
Using the multivariate adjustment (controlling for sociodemographic variables, lifestyle behavior, and health status),
higher initial levels of physical activity were significantly associated with better initial cognitive performance (standardized
coefficient P=0. 17). A higher level of physical activity at baseline was significantly related to slower decline in cognitive
performance, as compared with a lower level of activity (|3=0.22) . The authors conclude that physical activity in later life
is associated with slower age-related cognitive decline.
During the follow-up period, 158 participants developed dementia while 107 developed Alzheimer's disease. The
interaction between exercise and incident dementia or Alzheimer disease was found to be statistically significant. The
incidence rate of dementia was 1 3.0 per 1 ,000 person-years for participants who exercised 3 or more times per week,
compared with 1 9.7 per 1 ,000 person-years for those who exercised less than 3 times per week. Similar results were
observed in analyses for incident Alzheimer's disease.
The results showed that, compared with no exercise, physical activity was significandy associated with lower risks of cognitive
impairment of all types, including dementia and Alzheimer's disease. Furthermore, a significant dose-response relationship was
observed whereby greater physical activity was associated with increased protection for cognitive decline and disease.
A significant negative association (positive effect of exercise) between both low and high exercise and cognitive decline
was observed.
The results showed that older adults in the highest level of activity energy expenditure had lower odds of incident
cognitive impairment than those in the lowest levels of activity energy expenditure. Furthermore, a significant dose-
response relationship was observed between incident activity energy expenditure and incidence of cognitive impairment.
Eighty-two patients were available for analysis. The results showed no statistically significant difference between the
treatment or control groups in terms of cognitive function.
One hundred and twenty subjects were analyzed. In comparison with a no intervention group, Tai Chi and social
intervention showed an increase of brain volume via magnetic resonance imaging (P<0.05) and improvement in several
neuropsychological measures (P<0.05). No difference was observed between the walking and the no intervention group.
This result differs from the previous trials in that the increase of brain volume and cognitive function in the current study
is associated with nonaerobic exercise and social interaction.
One hundred and nine patients were available for analysis. A significant decrease in MMSE score in the control group was
observed, and the odds ratio for treated older adults having stable cognitive status one year later (as compared with the
control group) was 2.74, suggesting that a 1 2-month endurance exercise training program may delay the onset of age-
related cognitive decline in the elderly.
Resistance training participants had significantly improved performance on the Stroop Test, an executive cognitive test
of selective attention/conflict resolution and the associated memory task compared with subjects in a balance and tone
training group (P=0.04 and P=0.03, respectively). This study suggests that twice-weekly resistance training could alter the
trajectory of cognitive decline in seniors with mild cognitive impairment.
There were no significant differences between balance, sleep quality, and cognitive performance test. At the end of the
study, participants in the Tai Chi training group showed a significantly (P<0.00 1 ) higher Trail Making Test score in part A
(44.2±4.5 versus 35±4.3) and part B ( I 1 8.3±6.4 versus 1 02±5).
Participants in the highest quartile of physical energy expenditure had a relative risk of dementia of 0.85 compared with
those in the lowest quartile, and participants who participated in more than four physical activities had a relative risk of
dementia of 0.5 1 as compared with those who participated in 0 or I physical activities. Similar results were observed with
risk of Alzheimer's disease.
(Continued)
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Physical activity and cognitive function in individuals aged over 60 years
Table 3 {Continued)
Source and study
design
Results
Ravaglia et aP' Physical activity is associated w\th a lowered risk of vascular dementia, but not of Alzheimer's disease.
Prospective study
Scarmeas et al" During a mean of 5.4 years of follow-up, a total of 282 incident Alzheimer's disease cases occurred. The hazard ratio for
Prospective study some physical activity (compared with no physical activity) was 0.67, and for much physical activity was 0.67. This study
suggests that physical activity is associated with a reduced risk for Alzheimer's disease.
Schuit et aP'' Subjects with one hour or less of daily physical activity were at doubly increased risk of cognitive decline as compared
Prospective study with subjects who participated in more than one hour of physical activity daily. This study suggests that promotion of
physical activity at an advance aged may reduce the risk of cognitive decline.
Smiley-Oyen et aP' The results showed improvements in performance on the Stroop Color and Word Test only in the aerobic exercise
RCT group, and the study failed to show a dose-response relationship.
Taaffe et aP° For men with low physical function at baseline, high levels of exercise were associated with half the dementia risk as
Prospective study compared with men who were the least active. A moderate level of physical activity was found to be protective, because
the risk of dementia and Alzheimer's disease decreased significantly with higher levels of physical activity. However, the
study was not able to identify a correlation between dementia and Alzheimer's disease risk and physical activity in men
with moderate or high levels of physical activity at baseline.
Van Gelder et aP' While there was no difference in the rates of cognitive decline between men with a high or low duration of physical
Prospective study activity at baseline, it was observed that a decrease in physical activity duration >60 minutes per day over 10 years
resulted in a decline of 1.7 points in the MMSE. Further, men in the lowest physical activity intensity quartile had a 10-year
cognitive decline 1 .8 times greater than that observed in men in the higher physical activity intensity quartiles. This study
suggests that participation in physical activities of at least low-medium intensity in old age may delay the onset of cognitive
decline.
Wang et al'" During the 1 0-year period, 3 1 9 participants developed dementia and 22 1 developed Alzheimer's disease. The results
Prospective study showed that a one-point decrease in performance-based physical function test scores was associated with an increased
risk of dementia and Alzheimer's disease. This study suggests that poor physical function may lead to onset of dementia
and Alzheimer's disease, while higher levels of physical fitness may delay onset of cognitive decline and disease.
Wang et aP A high level of physical activity was related to less decline in episodic memory (P<O.OS) and language (P<O.OI). When
Prospective study mental, physical, and social activities were integrated into a composite activity index, a dose-response pattern was observed.
Williamson et al° Ninety participants were available for analysis at the end of the study. The results did not show a significant difference
RCT between the groups; however, improvements in cognitive test scores on the Digit Symbol Substitution Test, Rey Auditory
and Verbal Learning Test, and modified Stroop Test were associated with improvements in physical function.
Yaffe et al" Women with a greater baseline physical fitness level were less likely to undergo cognitive decline during the 6— 8-year
Prospective study follow-up period. A dose-response relationship was observed whereby cognitive decline occurred in 17%, 18%, 22%, and
24% of women in the highest, third, second, and lowest quartiles of physical activity as measured by blocks walked per
week. Similar results were obtained when analyzing quartiles of kilocalorie expenditure. This study suggests that women
with higher levels of baseline physical activity and fitness are less likely to develop cognitive decline.
Abbreviations: RBMT, Rivermead Behavioural Memory Test; RCT, randomized controlled trial; MMSE, Mini-Mental State Examination.
in learning and memory processes^"-^' suggests that cognitive
decline in aging may be associated with dysregulation of brain
plasticity.'^ Mahncke et al" demonstrated that elderly subjects
with normal cognitive function had enhancement of memory
following an intensive, plasticity -based computer training pro-
gram. Physical exercise^'' " promotes positive neuroplasticity,
increases cognitive reserve and higher neuronal connection
Table 4 Association betv/een physical activity and cognitive
function in selected studies
Level of association
Number of studies
References
Significant
26
8,10-24,26,27,55-62
Insignificant
1
9
No association
0
N/A
Total
27
(See above references)
Abbreviation: N/A, not applicable.
density, and results in improved cognitive fiinction. On the
contrary, negative neuroplasticity results from physical inac-
tivity, poor nutrition, substance abuse, and social isolation,
decreases cognitive reserve, and inhibits formation of neuronal
connections, leading to reduced cognitive function.'"'"
Cerebral blood flow
While both aerobic and isometric physical activity are thought
to confer improved cognition, studies suggest that aerobic
exercise may be more effective in slowing degenerative
neurological processes that lead to age-related cognitive
decline and dementia.'^ How might aerobic exercise contrib-
ute to neuroprotection? Many processes leading to cognitive
decline stem from atherosclerotic or cerebrovascular condi-
tions that produce cerebral hypoperfiision.^' Ruitenberg et al
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found that higher cerebral blood flow velocity was significantly
associated with less cognitive decline and lower velocity was
related to Alzheimer's disease.'*" The capacity of long-term
aerobic exercise to mitigate the effects of vascular disease
is well established,"" and may be an important mechanism
of cognitive preservation due to exercise. Other mechanisms
of neuronal enhancement with exercise include the role of
neurotransmitters, changes in brain vasculature, and effects of
neurotrophins.*^ *^ These processes, individually or together,
may attenuate neurodegeneration and confer neuroprotective
benefits, resulting in improved cognitive function.
Angiogenesis
Angiogenesis, the formation of vasculature by pre-existing
endothelial cells, occurs in the brain during development but
declines with age. Animal models have shown that exercise
induces angiogenesis of small-vessel vasculature in the cer-
ebellum, motor cortex, and hippocampus. Animal studies have
shown that the hippocampus, which is essential for memory
formation, is highly oxygen-dependent. Consequently, hip-
pocampal angiogenesis may explain improvements in learning
and memory following sustained, moderate-level physical
activity. Maximal oxygen consumption increases with aero-
bic exercise, which is thought to be effective in promoting
brain angiogenesis in experimental animals (rodents'*' and
monkeys'*^). Therefore, aerobic exercise may have more
impact on cognitive performance than isometric exercise.
Effects of cytokines, neurotrophins,
and brain volume
Neurotrophins are endogenous brain proteins that serve to
promote neuroplasticity, and are thought to play a central
role in response to physical activity. Granulocyte colony-
stimulating factor (G-CSF) and brain-derived neurotrophic
factor (BDNF) are implicated in mediating increases in
cerebral gray matter volume and hippocampal volume,
respectively,*^ and enhancing cognitive performance by
optimizing cognitive reserve, increasing learning capacity,
and streamlining memory processes.*^ The effect of G-CSF in
subjects undergoing exercise protocols has been evaluated in
several studies; plasma levels of G-CSF have been found to
increase significantly after short bursts of aerobic exercise*''
as well as following periods of endurance exercise.*' The role
of G-CSF on neutrophil activation, proliferation, and survival
is important for the immune response, thus illustrating the
possible correlation with exercise in immunomodulation.
BDNF is integral to differentiation, extension, and survival
of neurons in the hippocampus, cortex, and cerebellum
during brain development,**"^" and increases levels of syn-
aptophysin and synaptobrevin, substances that aid transport
of neurotransmitter vesicles. Support for this mechanism
comes from animal studies showing that regulation of
BDNF is associated with physical activity, as demonstrated
by increased BDNF gene expression in rats as a result of
running,^^^-'"' with diminished or nonapparent effects when
BDNF production is blocked. '^ The role of BDNF in cognitive
impairment remains inconclusive, with studies reporting
different results. Nevertheless, the importance of BDNF
in preservation and enhancement of cognitive function in
humans was demonstrated by Erickson et al,*^ who found
that decreased levels were associated with age-related decline
in hippocampal volume, and that aerobic exercise increased
BDNF, hippocampal and temporal lobe volumes, and spatial
memory. The association between BDNF level, hippocampal
volume, and dementia was also established at the molecular
level in subjects with BDNF gene polymorphism."
Conclusion
There is evidence suggesting that physical activity in later
life is beneficial for cognitive function in elderly persons.
These benefits include enhancement of existing cognitive
function and maintenance of optimal cognitive function, as
well as prevention or delayed progression of cognitive dis-
eases, such as Alzheimer's dementia or other neurocognitive
disorders. However, the majority of the evidence included
in this review was of medium quality, and the overall risk
of bias in the studies used in this review is moderately high.
Despite the variable quality of the evidence, most of the data
supports the concept that moderate-level physical activity in
late life may improve cognitive function and delay the onset
of debilitating cognitive disease in older persons. More evi-
dence obtained from larger RCTs, preferably lasting for at
least one year, is needed to confirm the association between
physical activity in late life and improvements in cognitive
function. Future research should focus on whether aerobic
or isometric physical activity has a greater effect on cogni-
tion in the elderly, and which cognitive domains are most
affected by physical activity. Additionally, research should
be directed toward identifying and implementing exercise
programs that would produce extended results on cognitive
function in elderly patients.
Acknowledgment
The authors acknowledge the Department of Veterans Affairs,
Queen's University Belfast and The John Butler Lung Foun-
dation for their support of this work.
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Physical activity and cognitive function in individuals aged over 60 years
Disclosure
The authors report no conflicts of interest in this work.
References
1 . Vance D, Wright M. Positive and negative neuroplasticity : implications
for age-relative cognitive declines. J Gerontol Nurs. 2009;35: 1 1-17.
2. Kinsella K, He W. An Aging World: 2008. US Census Bureau,
International Population Reports. Available from: http://www.census.
gov/prod/2009pubs/p95-09-l.pdf. Accessed January 6, 2009.
3. Wimo A, Winblad B, Johnsson L. The worldwide societal
costs of dementia: estimates for 2009. Alzheimers Dement.
2010;6:98-103.
4. Plassman BL, WilHams J, Burke JR, HolsingerT, Benjamin S. Systematic
review: factors associated with risk for and possible prevention of cogni-
tive decline in later Hfe. Ann Intern Med. 2010;153:182-193.
5. Maaike A, Geert A, Verhaar H, Aleman A, Luc V Physical activity
and enhanced fitness to improve cognitive function in older people
without known cognitive impairment. Cochrane Database Syst Rev.
2008;2:1-37.
6. Forbes D, Forbes S, Morgan DG, Markle-Reid M, Wood J,
Culum I. Physical activity programs for persons with dementia.
Cochrane Database Syst Rev. 2008;3 : 1-26.
7. Tseng CN, Gau BS, Lou MF. The effectiveness of exercise on improv-
ing cognitive function in older people: a systematic review. J Nurs Res.
2011;19:119-131.
8. Williamson JD, Espeland M, Kritchevsky SB, et al. Changes in cognitive
fiinction in a randomized trial of physical activity: results of the lifestyle
interventions and independence for elders pilot study. J Gerontol A Biol
SciMedSci. 2009;64A:688-694.
9. Miu DKY, Szeto SL, Mak YF. A randomized controlled trial on the
effect of exercise on physical, cognitive, and affective function in
dementia subjects. Asian J Gerontol Geriatr. 2008;3:8-16.
10. Klusmanny EversA, SchwarzerR, et al. Complex mental and physical
activity in older women and cognitive performance: a 6-month ran-
domized controlled trial. J Gerontol A Biol Sci Med Sci. 2010;65A:
680-688.
1 1 . Ku PW Stevinson C, Chen LJ. Prospective associations between leisure-
time physical activity and cognitive performance among older adults
across an 1 1-year period. J Epidemiol. 2012;22:230-237.
12. Laurin D, Verreault R, Lindsay J, MacPherson K, Rockwood K.
Physical activity and risk of cognitive impairment and dementia in
elderly persons. Arch Neurol. 2001;58:498-504.
13. Lytle ME, Vander Bill J, Pandav RS, Dodge HH, Ganguli M. Exercise
level and cognitive decline: the MoVIES project. Alzheimer Dis Assoc
Dirarrf. 2012;18:57-64.
14. Middleton LE, Manini TM, Simonsick EM, et al. Activity energy
expenditure and incident cognitive impairment in older adults. Arch
Intern Med 2011;171:1251-1257.
15. Wang HX, Jin Y, Hendrie HC, et al. Late life leisure activities
and risk of cognitive decline. / Gerontol A Biol Sci Med Sci.
2012;68:205-213.
16. Yaffe K. A prospective study of physical activity and cognitive decline
in elderly women: women who walk. Arch Intern Med. 2001; 161:
1703-1708.
17. Busse AL, Filho W Magaldi R, et al. Effects of resistance train-
ing exercise on cognitive performance in elderly individuals
with memory impairment: results of a controlled trial. Einstein.
2008;6:402-407.
18. Cassilhas R, Viana Y, Grassmami V, et al. The impact of resistance
exercise on the cognitive function of the elderly. Med Sci Sports Exerc.
2007;39:1401-1407.
19. Mortimer JA, Ding D, Borenstein AR, et al. Changes in brain volume
and cognition in a randomized trial of exercise and social interac-
tion in a community-based sample of non-demented Chinese elders.
J Alzheimers Dis. 2012;30:757-766.
20. Muscari A, Giaimoni C, Pierpaoli L, et al. Chronic endurance exercise
training prevents aging-related cognitive decline in healthy older
adults: a randomized controlled trial. Int J Geriatr Psychiatry. 2010;25:
1055-1064.
2 1 . Smiley-Oyen A, Lowry K, Francois S, Kohut M, Ekkekakis P. Exercise,
fitness, and neurocognitive function in older adults: the selective
improvement and cardiovascular fitness hypotheses. Ann Behav Med.
2008;36:280-291.
22. Buchman AS, Boyle PA, Yu L, Shah RC, Wilson RS, Bennett DA. Total
daily physical activity and the risk of AD and cognitive decline in older
aduhs. Neurology. 2012;78:1323-1329.
23 . Ravaglia G, Forti P, Lucicesare APN, Rietti E, Bianchin M, Dalmonte E.
Physical activity and dementia risk in the elderly: findings from a
prospective Italian study. Neurology. 2008;70:1786-1794.
24. Schuit AJ, Feskens EJ, Launer LJ, Kromhout D. Physical activity and
cognitive decline, the role of the apolipoprotein e4 allele. Med Sci Sports
Exerc. 2001;33:772-777.
25. van Praag H, Shubert T, Zhao C, Gage FH. Exercise enhances learn-
ing and hippocampal neurogenesis in aged mice. JNeurosci. 2005;25:
8680-8685.
26. Nagamatsu LS, Ma H, Hsu T. Resistance training promotes cognitive
and functional brain plasticity in seniors with probable mild cognitive
impairment. Arch Intern Med. 2012;172:666-668.
27. Nguyen MH, Kruse A. A randomized controlled trial of Tai chi for bal-
ance, sleep quality and cognitive performance in elderly Vietnamese.
Clin Interv Aging. 2012;7:185-190.
28. Segal SK, Cotman CW, Cahill LF. Exercise-induced noradrenergic
activation enhances memory consolidation in both normal aging and
patients with amnestic mild cognitive impairment. J Alzheimers Dis.
2012;32:1011-1018.
29. Hoffman B, Blumenthal J, Babyak M, et al. Exercise fails to improve
neurocognition in depressed middle-aged and older adults. Med Sci
Sports Exerc. 2008;40:1344-1352.
30. Caroni P, Donate F, MuUer D. Structural plasticity upon learning:
regulation and functions. Nat Re\' Neurosci. 2012; 13:478-490.
31. DeCarli C, Kawas C, Morrison JH, Reuter-Lorenz PA, Sperling RA,
Wright CB. Session II: Mechanisms of age-related cognitive change
and targets for intervention: neural circuits, networks, and plasticity.
JGerontolA Biol Sci Med Sci. 2012;67:747-753.
32. Desai AK. Revitalizing the aged-brain. Med Clin North Am. 201 1;95:
463^75.
33. Mahncke HW, Connor BB, Appelman J, et al. Memory enhance-
ment in healthy older adults using a brain plasticity-based training
program: a randomized, controlled study. Proc Natl Acad Sci USA.
2006;103:12523-12528.
34. Colcombe SJ, Kramer AF, Erickson KI, et al. Cardiovascular fitness,
cortical plasticity, and aging. Proc Natl Acad Sci USA. 2004;101:
3316-3321.
35. PangTYC, HannanAJ Enhancement of cognitive fiinction in models of
brain disease through environmental enrichment and physical activity.
Neuropharmacology. 2013;64:515-528.
36. Hall CB, Lipton RB, Sliwinski M, Katz MJ, Derby CA, Verghese J.
Cognitive activities delay onset of memory decline in persons who
develop dementia. Neurology. 2009;73:365-361.
37. Howes MJ, Perry E. The role of phytochemicals in the treatment and
prevention of dementia. Drugs Aging. 201 1;28:439^68.
38. Ahlskog JE, Geda YE, Graff-Radford NR, Petersen RC. Physical exer-
cise as a preventive or disease-modifying treatment of dementia and
brain aging. Mayo Clin Proc. 201 1;86:876-884.
39. Lojovich JM. The relationship between aerobic exercise and cognition:
is movement medicinal? J Head Trauma Rehabil. 20 10;25: 184-192.
40. Ruitenberg A, den Heijer T, Bakker SLM, et al. Cerebral hypoperfia-
sion and clinical onset of dementia: The Rotterdam study. Ann Neurol.
2005;57:789-794.
41. Heran BS, Chen JM, Ebrahim S, et al. Exercise-based cardiac reha-
bilitation for coronary heart disease. Cochrane Database Syst Rev.
201I;7:CD001800.
Clinical Interventions in Aging 2014:9
submit your manuscript | www.dovepi ess.corr
Dovepress
677
Carvalho et al
Doveoress
42. Ploughman M. Exercise is brain food: tlie effects of pliysical activity
on cognitive fiinction. Dev Neurorehahil. 2008; 1 1 :236-240.
43. Rhyu IJ, Bytlieway JA, Koliler SJ, et al. Effects of aerobic exercise
training on cognitive function and cortical vascularity in monkeys.
Neuroscience. 2010;167:1239-1248.
44. Erickson Kl, Voss MW, Prakash RS, et al. Exercise training increases
size of hippocampus and improves memory. Proc Natl Acad Sci USA.
2011;108:3017-3022.
45. Erickson KI, Prakash RS, Voss M, et al. Brain-derived neurotrophic
factor is associated with age-related decline in hippocampal volume.
JNeurosci. 2010;30:5368-5375.
46. Yamada M, Suzuki K, Kudo S, Totsuka M, Nakaji S, Sugawara K. Raised
plasma G-CSF and lL-6 after exercise may play a role in neutrophil mobi-
lization into the circulation. J Appl Physiol (1985). 2002;92:1789-1794.
47. Suzuki K, Yamada M, Kurakake S, et al. Circulating cytokines and
hormones with immunosuppressive but neutrophil-priming poten-
tials rise after endurance exercise in humans. Eur J Appl Physiol.
2000;81:281-287.
48. Johnson RA, Rhodes JS, Jeffrey SL, Garland T Jr, Mitchell OS.
Hippocampal brain-derived neurotrophic factor but not neurotrophin-3
increases more in mice selected for increased voluntary wheel running.
Neuroscience. 2003;121:1-7.
49. Richter-Schmidinger T, Alexopoulos P, Horn M, et al. Influence of
brain-derived neurotrophic-factor and apolipoprotein E genetic variants
on hippocampal volume and memory performance in healthy young
adults. J Neural Transm. 201 1;1 18:249-257.
50. Webster MJ, Herman MM, Kleinman JE, Shannon Weickert C. BDNF
and trkfl mRNA expression in the hippocampus and temporal cortex
during the human lifespan. Gene Expr Patterns. 2006;6:941-951.
51. Vaynman S, Ying Z, Gomez-Pinilla F. Hippocampal BDNF mediates
the efficacy of exercise on synaptic plasticity and cognition. Eur J
Neurosci. 2004;20:2580-2590.
52. Borroni B, Bianchi M, Premi E, et al. The brain-derived neurotrophic
factor Val66Met polymorphism is associated with reduced hippocam-
pus perfusion in frontotemporal lobar degeneration. JAlzheimers Dis.
2012;31:243-251.
53. Coen RF, Lawlor BA, Kenny R. Failure to demonstrate that memory
improvement is due either to aerobic exercise or increased hippocampal
m\ume. Proc Natl Acad Sci USA. 201 1;108:E89.
54. DriscoU 1, Martin B, An Y, et al. Plasma BDNF is associated with age-
related white matter atrophy but not with cognitive function in older,
non-demented adults. PLoS One. 2012;7:e35217.
5 5 . Larson EB, Wang L, Bowen JD, et al. Exercise is associated with reduced
risk for incident dementia among persons 65 years of age and older
Ann Intern Med. 2006;144:73-81.
56. Podewils LJ, Guallar E, Kuller LH, et al. Physical activity, APOE
genotype, and dementia risk: findings from the Cardiovascular Health
Cognition Study Am J Epidemiol. 2005;161:639-651.
57. Scarmeas N. Physical activity, diet, and risk of Alzheimer disease.
JAMA. 2009;302:627-637.
58. Taaffe DR, Irie F, Masaki KH, et al. Physical activity, physical fiinction,
and incident dementia in elderly men: the Honolulu- Asia Aging Study.
J Gerontol A Biol Sci Med Sci. 2008;63:529-535.
59. van Gelder BM, Tijhuis MAR, Kalmijn S, Giampaoli S, Nissinen A,
Kromhout D. Physical activity in relation to cognitive decline in elderly
men: the FINE shady Neurology. 2004;63:2316-2321.
60. Wang L. Performance-based physical fiinction and fiifiire dementia in
older people. Arch Intern Med. 2006;166: 1 1 15-1 120.
61. Geda YE, Roberts R, Knopman D, et al. Physical exercise, aging, and
mild cognitive impairment: a population-based study. Arch Neurol.
2010;67:80-86.
62. Bixby WR, Spalding TW, Haufier A, et al. The unique relation of
physical activity to executive fiinction in older men and women. Med
Sci Sports Exerc. 2007;39:1408-1416.
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Physical activity and cognitive function in individuals aged over 60 years
Supplementary material
Table SI Agency for Healthcare Research and Quality Methods
summary ratings of quality of individual studies
Good (low risk These studies have the least bias and results are
of bias) considered valid. A study that adheres mosdy to the
commonly held concepts of high quality including the
following: a formal randomized controlled design; clear
description of the population, setting, interventions,
and comparison groups; appropriate measurement of
outcomes; appropriate statistical and analytic methods
and reporting; no reporting errors; low dropout rate
and clear reporting of dropouts.
Fair These studies are susceptible to some bias, but it is
not sufficient to invalidate the results. They do not
meet all the criteria required for a rating of good
quality because they have some deficiencies, but
no flaw is likely to cause major bias. The study may
be missing information, making it difficult to assess
limitations and potential problems.
Poor (high risk These studies have significant flaws that imply biases
of bias) of various types that may invalidate the results.
They have serious errors in design, analysis, or
reporting; large amounts of missing information;
or discrepancies in reporting.
Source: Agency for Healtiicare Research and Quality Methods Reference Guide for
Effectiveness and Comparative Effectiveness Reviews ( http://vvww.ahrq.gOv/ V
Table S2 Characteristics of excluded studies
Andel et al'
Baker et aP
Barnes et al'
Brown et al""
Chang et al^
Colcombe et al'
Devore et al'
Etgen et al"
Fabre et al'
Floel etal'"
Gillum et al"
Hassett et aP
Kasai et al'^
Lautenschlager et al'"*
Liu-Ambrose et aP
McAuley et al"
McAuley et al"
Netz et al"
O'Dwyer et al"
Ojofeitimi et aP°
Parekh et aP'
Rovio et al^^
Rovio et al"
Scherder et aP"*
Shubert et aP'
Vercambre et aP'
The study examines the effect of mid-life, not
late-life, physical activity on cognition.
Participants were too young to meet the given
inclusion criteria of this review.
Participants were too young to meet the given
inclusion criteria of this review.
The study contained too few participants and
participants were too young to meet the given
inclusion criteria of this review.
Examines the effect of mid-life, not late-life,
physical activity on cognition.
The study contained too few participants and
participants were too young to meet the given
inclusion criteria of this review.
Participants were too young to meet the given
inclusion criteria of this review.
Participants were too young to meet the given
inclusion criteria of this review.
The duration of the study was too short to
meet the given inclusion criteria of this review.
Participants were too young to meet the given
inclusion criteria of this review.
The outcome measure was death; this does not
meet the given inclusion criteria for this review.
Participants were patients who had suffered
traumatic brain injury; this was an exclusion
criterion for the review.
The study contained too few participants to
meet the given inclusion criteria of this review.
Participants were too young to meet the given
inclusion criteria of this review.
Participants were elderly patients who had
specifically suffered falls; this was an exclusion
criterion for the review.
The study contained too few participants and
participants were too young to meet the given
inclusion criteria of this review.
Outcome measures included social-relation
capacity and well-being; this does not meet the
given inclusion criteria for this review.
Participants were too young to meet the given
inclusion criteria of this review.
The duration of the trial was too short to meet
the given inclusion criteria of this review.
Participants were too young to meet the given
inclusion criteria for this review.
Participants were patients with lung disease;
this was an exclusion criterion for this review.
The study examines the effect of mid-life, not
late-life, physical activity.
The study examines the effect of mid-life, not
late-life, physical activity.
The duration of the trial was too short to meet
the given inclusion criteria for this review.
The duration of the trial was too short to meet
the given inclusion criteria for this review.
Participants were patients specifically with
vascular disease; this was an exclusion criterion
for the review.
(Continued)
Clinical Interventions in Aging 2014:9
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Carvalho et al
Table S2 {Continued)
Verghese et al"
The study examines the effect of cognitive, not
physical, leisure activities on late-life cognition.
Voelcker-Rehage
The study contained too few participants to
et aP=
meet the given inclusion criteria for this review.
Weuve et aP'
Participants were too young to meet the given
inclusion criteria for this review.
Wolinsky et al^"
The study examines the effect of cognitive, not
physical, activities on late-life cognition.
Doveore<;s
Table S3 Grouping of cognitive tests and studies of cognitive function
Cognitive domain
Name of test
References
Cognitive speed
Immediate verbal memory
function
Global cognitive function
Cognitive inhibition
Working memory
Differentiation between dementia
and Alzheimer's disease
Verbal/nonverbal intelligence
Sustained attention
Presence of dementia
Presence of Alzheimer's disease
Executive function
Simple reaction time
8-Choice reaction time
Go/no-go reaction time
Digit symbol substitution test
Trail making test
Wechsler Adult Intelligence Scale
The Rey Auditory Verbal Learning Test
Mini-Mental State Examination
Modified Mini-Mental State Examination
Stroop Color and Word Test
Direct and Indirect Digit Span
Rivermead Behavioral Memory Test
Memory Complaints Scale
Cambridge Cognitive Test
Kaufman Brief Intelligence Test
Toulouse-Pieron Concentration Attention Test
Cognitive Abilities Screening Instrument
Informant Questionnaire on Cognitive Decline in the Elderly
Community Screening for Dementia
Alzheimer's Disease Assessment Scale-Cognitive Subscale
Mental Deterioration Battery
Wisconsin Card Sort Test
Rey-Osterrieth Complex Figure Test
Smiley-Oyen et al^'
Smiley-Oyen et al^'
Smiley-Oyen et al^'
Williamson et al"
Klusmann et al," Nguyen et al,''' Nagamatsu et al'^
Busse et al^'
Williamson et al"
Lyde et al," Miu et al,'° Muscari et al,"
Ravaglia et al,* Schuit et al,"' Van Gelder et al,"^
Williamson et al," Laurin et al,* Klusmann et al'^
Middleton et al,"" Podewils et al,"= Yaffe et al"'
Bixby et al,"' Smiley-Oyen et al,''
Williamson et al," Nagamatsu et al'^
Busse et al"
Busse et al"
Cassilhas et al,"° Busse et aP'
Busse et aP'
Bixby et al"'
Cassilhas et al"°
Taaffe et al,"' Wang et aP'
Taaffe et a!"'
Wang et aP"
Miu et aP'
Ravaglia et al""
Smiley-Oyen et aP'
Williamson et al," Wang et aP'
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Clinical Interventions in Aging 2014:9
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References
1 . Andel R, Crowe M, Pedersen NL, Fratiglioni L, Johansson B, Gatz M.
Physical exercise at midlife and risk of dementia three decades later:
a population-based study of Swedish twins. J Gerontol A Biol Sci Med
Sci. 2008;63(l):62-66.
2. Baker LD, Frank LL, Foster-Schubert K. Effects of aerobic exer-
cise on mild cognitive impairment: a controlled trial. Arch Neurol.
2010;67(l):71-79.
3. Barnes DE, Yaffe K, Satariano WA, Tager IB. A longitudinal study of
cardiorespiratory fitness and cognitive function in healthy older adults.
J Am GeriatrSoc. 2003;51 :459^65.
4. Brown AD, McMorris CA, Longman RS, et al. Effects of cardiorespi-
ratory fitness and cerebral blood tlow on cognitive outcomes in older
women. Neiirohiol Aging. 2010;31:2047-2057.
5. Chang M, Jonsson ?\, Snaedal J, et al. The effect of midlife physical
activity on cognitive function among older adults: AGES-Reykjavik
Study J Gerontol A Biol Sci Med Sci. 2010;65:1369-1374.
6. Colcombe SJ, Kramer AF, Erickson KI, et al. Cardiovascular fit-
ness, cortical plasticity, and aging. Proc Natl Acad Sci USA. 2004;
101:3316-3321.
7. Devore EE, Kang JH, Okereke 0, Grodstein F. Physical activity
levels and cognition in women with type 2 diabetes. Am J Epidemiol.
2009;170:1040-1047.
8. Etgen T, Sander D, Huntgeburth U, Poppert H, Forstl H, Bickel H.
Physical activity and incident cognitive impairment in elderly persons:
the INVADE study Arch Intern Med. 2010;170:186-193.
9. Fabre C, Chamari K, Mucci P, Masse-Biron J, Prefaut C. Improvement
of cognitive fiinction by mental and/or individualized aerobic training
in healthy elderly subjects. International Journal of Sports Medicine
2002;23:415^21.
10. Floel A, Ruscheweyh R, Kruger K, et al. Physical activity and memory
functions: are neurotrophins and cerebral gray matter volume the miss-
ing lh±T Neuroltnage. 2010;49:2756-2763.
1 1 . Gillum RF, Obisesan TO. Physical activity, cognitive function, and
mortality in a US national cohort. Ann Epidemiol. 2010;20:251-257.
12. Hassett LM, Moseley AM, Tate R, Harmer AR. Fitness training for
cardiorespiratory conditioning after traumatic brain injury. Cochrane
Database Syst Rev. 2008;CD006123.
13. Kasai JYT, Busse AL, Magaldi RM, et al. Effects of Tai Chi Chuan on
cognition of elderly women with mild cognitive impairment. Einstein
(16794508) 20lO;&:40-45.
14. Lautenschlager NT, Cox KL, Flicker L, et al. Effect of physical activity
on cognitive function in older adults at risk for Alzheimer disease: a
randomized trial. JAMA. 2008;300: 1027-1037.
15. Liu-Ambrose T, Donaldson MG, Ahamed Y, et al. Otago home-based
strength and balance retraining improves executive functioning
in older fallers: a randomized controlled trial. J Am Geriatr Soc.
2008;56:1821-1830.
16. McAuley E, Szabo AN, Mailey EL, et al. Non-exercise estimated
cardiorespiratory fitness: associations with brain structure, cognition,
and memory complaints in older adults. Ment Health Phys Act. 2011;
4:5-11.
17. McAuley E, Blissmer B, Marquez DX, Jerome GJ, Kramer AF,
Katula J. Social relations, physical activity, and well-being in older
adults. Prev Med. 2000;3 1 :608-6 17.
18. NetzY, Argov E, Inbar O. Fitness's moderation of the facilitative effect
of acute exercise on cognitive flexibility in older women. J Aging Phys
Act. 2009;17:154-166.
19. O'Dwyer ST, Burton NW, Pachana NA, Brown WI Protocol for Fit
Bodies, Fine Minds: a randomized controlled trial on the affect of
exercise and cognitive training on cognitive ftmctioning in older adults.
BMC Geriatr 2007;7:23.
20. Ojofeitimi EO, Ijadunola KT, Jegede VA, et al. Nutritional status and
physical activity in relation to cognitive fiinction in a group of elderly
in Nigeria. Journal of Nutrition For the Elderly. 2002;22:49-62.
Physical activity and cognitive function in individuals aged over 60 years
21. Parekli PI, Blumenthal JA, Babyak MA, et al. Gas exchange and exer-
cise capacity affect neurocognitive performance in patients with lung
disease. Psychosom Med. 2005;67:425^32.
22. Rovio S, Kareholt I, Helkala EL, et al. Leisure-time physical activity
at midlife and the risk of dementia and Alzheimer's disease. Lancet
Neurol. 2005;4:705-711.
23 . Rovio S, Kareholt I, Viitanen M, et al. Work-related physical activity and
the risk of dementia and Alzheimer's disease. IntJ Geriatr Psychiatry.
2007;22:874-882.
24. Scherder EJ, Van Paasschen J, Deijen JB, et al. Physical activity and
executive fimctions in the elderly with mild cognitive impairment. Aging
Ment Health. 2005;9:272-280.
25. Shubert TE, McCulloch K, Hartman M, Giuliani CA. The effect of
an exercise-based balance intervention on physical and cognitive
performance for older adults: a pilot study. / Geriatr Phys Ther.
2010;33:157-164.
26. Vercambre MN, Grodstein F, Manson JE, Stampfer MJ, Kang JH.
Physical activity and cognition in women with vascular conditions.
Arch Intern Med 201 1;171:1244-1250.
27. Verghese J, Lipton RB, Katz MJ, et al. Leisure activities and the risk of
dementia in the elderly N Engl J Med. 2003;348:2508-2516.
2 8 . Voelcker-Rehage C, Godde B, Staudinger UM. Physical and motor fitness are
both related to cognition in old age. Euro J Neurosci. 2010;31:167-176.
29. Weuve J, Kang JH, Manson JE, Breteler MM, Ware JH, Grodstein E
Physical activity, including walking, and cognitive function in older
women. JAMA. 2004;292:1454-1461.
30. Wolinsky FD, Unverzagt FW, Smith DM, Jones R, Wright E,
Tennstedt SL. The effects of the ACTIVE cognitive training trial on
clinically relevant declines in health-related quality of life. J Gerontol
B Psychol Sci Soc Sci. 2006;61:S281-S287.
3 1 . Smiley-Oyen AL, Lowry KA, Francois SJ, Kohut ML, Ekkekakis P.
Exercise, fitness, and neurocognitive fiinction in older adults: the "selec-
tive improvemenf and "cardiovascular fitness" hypotheses. Ann Behav
Med. 2008;36:280-291.
32 . Williamson JD, Espeland M, Kritchevsky SB, et al. Changes in cognitive
ftinction in a randomized trial of physical activity: results of the lifestyle
interventions and independence for elders pilot study. J Gerontol A Biol
Sci Med Sci. 2009;64:688-694.
33. Klusmann V, Evers A, Schwarzer R, et al. Complex mental and
physical activity in older women and cognitive performance:
a 6-month randomized controlled trial. J Gerontol A Biol Sci Med Sci.
2010;65:680-688.
34. Nguyen MH, Kruse A. A randomized controlled trial of Tai chi for bal-
ance, sleep quality and cognitive performance in elderly Vietnamese.
Clin Interv Aging 2012;7:185-190.
35. NagamatsuLS, Handy TC, HsuCL, VossM, Liu- Ambrose T. Resistance
training promotes cognitive and functional brain plasticity in seniors
with probable mild cognitive impairment. Arch Intern Med. 2012;
172:666-668.
36. Busse AL, Filho WJ, Magaldi RM, et al. Effects of resistance training
exercise on cognitive performance in elderly individuals with memory
impairment: results of a controlled trial. Einstein. 2008;6:402^07.
37. Lytle ME, Vander Bilt J, Pandav RS, Dodge HH, Ganguli M. Exercise
level and cognitive decline: the MoVIES project. Alzheimer Dis Assoc
Disord. 2004;18:57-64.
38. MiuDKY, Szeto SL,MakYF. A randomized controlled trial on the effect
of exercise on physical, cognitive, and affective function in dementia
subjects. Asian J Gerontol Geriatr. 2008;3:8-16.
39. Muscari A, Giannoni C, Pierpaoli L, et al. Chronic endurance exer-
cise training prevents aging-related cognitive decline in healthy
older adults: a randomized controlled trial. Int J Geriatr Psychiatry.
2010;25:1055-1064.
40. Ravaglia G, Forti P, Lucicesare A, et al. Physical activity and dementia
risk in the elderly: findings from a prospective Italian study. Neurology.
2008;70:1786-1794.
Clinical Interventions in Aging 2014:9
submit your manuscript | www.dovepi ess.con i
Dovepress
681
Carvalho et al
Doveore<;s
41. Schuit AJ, Feskens EJ, Launer LJ, Kiomhout D. Physical activity and 47. Bixby WR, Spalding TW, Haufler AJ, et al. The unique relation of
cognitive decline, the role of the apolipoprotein e4 allele. Med Sci Sports physical activity to executive function in older men and women. Med
Exerc. 2001;33:772-777. Sci Sports Exerc. 2007;39:1408-1416.
42. van Gelder BM, Tijhuis MA, Kalmijn S, Giampaoli S, Nissinen A, 48. Cassilhas RC, Viana VA, GrassmannY et al. The impact of resistance
Kromhout D. Physical activity in relation to cognitive decline in elderly exercise on the cognitive function of the elderly. Med Sci Sports Exerc.
men: the FINE Study Neurology. 2004;63:2316-2321. 2007;39:1401-1407.
43. Laurin D, Verreault R, Lindsay J, MacPherson K, RockwoodK. Physical 49. Taaffe DR, Irie F, MasakiKH, et al. Physical activity, physical fiinction,
activity and risk of cognitive impairment and dementia in elderly and incident dementia in elderly men: the Honolulu- Asia Aging Study.
peraona. Arch Neurol. 2001;58:498-504. J Gerontol A Biol Sci Med Sci. 2008;63:529-535.
44. Middleton LE, Manini TM, Simonsick EM, et al. Activity energy 50. Wang L, Larson EE, Bowen JD, van Belle G. Performance-based
expenditure and incident cognitive impairment in older adults. Arch physical function and future dementia in older people. ^/r/i/wterHMerf.
Intern Med 2011;171:1251-1257. 2006;166:1115-1120.
45. Podewils LJ, Guallar E, Kuller LH, et al. Physical activity, APOE 51. Wang HX, Jin Y, Hendrie HC, etal. Late life leisure activities and risk of
genotype, and dementia risk: findings from the Cardiovascular Health cognitive decline. J Gerontol A Biol Sci Med Sci. 2013;68:205-213.
Cognition Study Am J Epidemiol. 2005;161:639-651.
46. Yaffe K. A prospective study of physical activity and cognitive decline
in elderly women: Women who walk. Archives of Internal Medicine
2001;161:1703-1708.
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